Study Comparing Daratumumab, Lenalidomide, Bortezomib, and Dexamethasone (D-RVd) Versus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Subjects With Newly Diagnosed Multiple Myeloma

NCT02874742 | Completed Phase 2 Results DMC

• 2 other identifiers: CR10819554767414MMY2004
• Study Type: interventional
• Target: 224
• Locations: 1 country
• Sites: 36

Brief Summary

The purpose of this study is to determine if the addition of daratumumab to lenalidomide-bortezomib-dexamethasone (RVd) will increase the proportion of participants achieving stringent complete response (sCR), as defined by the International Myeloma Working Group (IMWG) criteria, by the time of completion of post autologous stem cell transplantation (ASCT) consolidation treatment, compared with RVd alone.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Stringent Complete Response (sCR)

  Percentage of participants who had achieved sCR as determined by the validated computer algorithm according to the International Myeloma Working Group (IMWG) criteria, by the end of post-autologous stem cell transplantation (post-ASCT) consolidation treatment were reported. Complete response (CR) is defined as negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and less than (\<) 5 percent (%) PCs in bone marrow. sCR is defined as in addition to CR a normal FLC ratio, and absence of clonal plasma cells (PCs) by immunohistochemistry or immunofluorescence or 2 to 4-color flow cytometry.

  From randomization to post-ASCT consolidation (after Cycle 6) before maintenance treatment (up to 10 months)

Secondary Outcomes (15)

• Percentage of Participants With Complete Response (CR) or Better

  From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and at the end of maintenance period of 24 months (overall duration up to 34 months)

• Percentage of Participants With Overall Stringent Complete Response (sCR)

  From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and at the end of maintenance treatment of 24 months (overall duration up to 34 months)

• Percentage of Participants With Overall Response Rate (ORR)

  From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and at the end of maintenance treatment of 24 months (overall duration up to 34 months)

• Percentage of Participants Who Achieved Very Good Partial Response (VGPR) or Better

  From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and at the end of maintenance period of 24 months (overall duration up to 34 months)

• Percentage of Participants With Negative Minimal Residual Disease (MRD)

  From randomization to end of following: induction treatment, post-ASCT consolidation (after Cycle 6) (up to 4.5 months), and at the end of maintenance period of 24 months (overall duration up to 34 months)

Study Arms (2)

Daratumumab+Lenalidomide+Bortezomib+Dexamethasone (D-RVd)

EXPERIMENTAL

Participants will receive lenalidomide, bortezomib, dexamethasone and daratumumab.

Drug: Lenalidomide; Drug: Bortezomib; Drug: Dexamethasone; Drug: Daratumumab

Lenalidomide+Bortezomib+Dexamethasone (RVd)

EXPERIMENTAL

Participants will receive lenalidomide, bortezomib and dexamethasone.

Drug: Lenalidomide; Drug: Bortezomib; Drug: Dexamethasone

Interventions

Lenalidomide DRUG

Cycles 1 through 6: lenalidomide 25 (milligram) mg orally on Days 1 through 14 and each cycle is of 21-days followed by maintenance treatment with lenalidomide 10 mg on days 1-21 throughout each 28-day cycle on Cycles 7 through 9. Beginning at Cycle 10, the lenalidomide dose will be increased to 15 mg unless there is a tolerability concern.

Daratumumab+Lenalidomide+Bortezomib+Dexamethasone (D-RVd); Lenalidomide+Bortezomib+Dexamethasone (RVd)

Bortezomib DRUG

Bortezomib 1.3 mg/m\^2 subcutaneously on Days 1, 4, 8, and 11 during Cycles 1-6.

Daratumumab+Lenalidomide+Bortezomib+Dexamethasone (D-RVd); Lenalidomide+Bortezomib+Dexamethasone (RVd)

Dexamethasone DRUG

Dexamethasone 40 mg orally every week (20 mg on Days 1, 2, 8, 9, 15, and 16).

Daratumumab+Lenalidomide+Bortezomib+Dexamethasone (D-RVd); Lenalidomide+Bortezomib+Dexamethasone (RVd)

Daratumumab DRUG

Daratumumab intravenously at a dose of 16 milligram per kilogram (mg/kg) weekly during induction treatment (Days 1, 8, and 15 of Cycles 1 through 4), and every 3 weeks during consolidation treatment (Day 1 of Cycles 5 and 6), followed by maintenance treatment with daratumumab every 4 or 8 weeks.

Daratumumab+Lenalidomide+Bortezomib+Dexamethasone (D-RVd)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Considered by the investigator to be eligible for high-dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT) according to the institution's criteria based on age, medical history, cardiac and pulmonary status, overall health and condition, co-morbid condition(s), physical examination, and laboratory studies
• Has not had prior systemic therapy for multiple myeloma. An emergency course of steroids (defined as no greater than 40 milligram \[mg\] of dexamethasone, or equivalent per day for a maximum of 4 days (that is, a total of 160 mg) is permitted. In addition, radiation therapy is permitted prior to study entry, during screening, and during Cycles 1-2 of study treatment as needed for lytic bone disease
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
• Woman of childbearing potential must have 2 negative highly sensitive serum (beta-human chorionic gonadotropin \[b-hCG\]) during screening, the first one within 10 to 14 days prior to the first dose of any component of study treatment and the second within 24 hours prior to the first dose of any component of study treatment
• A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study (including during dose interruptions), and for 4 weeks following discontinuation of lenalidomide, and if receiving daratumumab, for 3 months after the last dose

You may not qualify if:

• Diagnosed or treated for malignancy other than multiple myeloma, except: a) Malignancy treated with curative intent and with no known active disease present for more than equal to (\>= )3 years before randomization; b) Adequately treated non-melanoma skin cancer, lentigo maligna or in situ malignancies (including but not limited to, cervical, breast) with no evidence of disease
• Exhibiting clinical signs of or has a known history of meningeal or central nervous system involvement by multiple myeloma
• Known chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) less than (\<)50 percent (%) of predicted normal
• Known moderate or severe persistent asthma within the past 2 years or currently has uncontrolled asthma of any classification
• Known to be seropositive for human immunodeficiency virus, known to have hepatitis B surface antigen positivity, or known to have a history of hepatitis C. Participants who completed treatment for hepatitis C at least 6 months prior to screening and have no detectable circulating hepatitis C virus (HCV) at screening, may participate in the study. Such participants will be required to undergo regular assessment for HCV reactivation during their participation in the study. Participants who test positive for HCV at any time during these assessments will be withdrawn from the study

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (36)

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Birmingham, Alabama, United States

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Duarte, California, United States

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La Jolla, California, United States

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Los Angeles, California, United States

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San Francisco, California, United States

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Aurora, Colorado, United States

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Washington D.C., District of Columbia, United States

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Orlando, Florida, United States

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Tampa, Florida, United States

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Atlanta, Georgia, United States

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Chicago, Illinois, United States

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Westwood, Kansas, United States

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New Orleans, Louisiana, United States

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Baltimore, Maryland, United States

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Boston, Massachusetts, United States

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Worcester, Massachusetts, United States

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Detroit, Michigan, United States

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St Louis, Missouri, United States

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Omaha, Nebraska, United States

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Buffalo, New York, United States

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New York, New York, United States

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Chapel Hill, North Carolina, United States

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Charlotte, North Carolina, United States

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Durham, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Columbus, Ohio, United States

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Portland, Oregon, United States

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Abington, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Nashville, Tennessee, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Salt Lake City, Utah, United States

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Seattle, Washington, United States

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Spokane, Washington, United States

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Milwaukee, Wisconsin, United States

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Related Publications (11)

• Voorhees PM, Sborov DW, Laubach J, Kaufman JL, Reeves B, Rodriguez C, Silbermann R, Costa LJ, Anderson LD Jr, Nathwani N, Shah N, Bumma N, Efebera YA, Holstein SA, Costello C, Jakubowiak A, Wildes TM, Orlowski RZ, Shain KH, Cowan AJ, Dinner S, Gries KS, Pei H, Cortoos A, Patel S, Lin TS, Usmani SZ, Richardson PG. A plain language summary of the final analysis of the GRIFFIN study of daratumumab plus lenalidomide, bortezomib, and dexamethasone for people with newly diagnosed multiple myeloma. Future Oncol. 2025 Jan;21(1):25-49. doi: 10.1080/14796694.2024.2408909. Epub 2024 Oct 25.

  PMID: 39452950 DERIVED

• Sonneveld P, Dimopoulos MA, Boccadoro M, Quach H, Ho PJ, Beksac M, Hulin C, Antonioli E, Leleu X, Mangiacavalli S, Perrot A, Cavo M, Belotti A, Broijl A, Gay F, Mina R, van de Donk NWCJ, Katodritou E, Schjesvold F, Balari AS, Rosinol L, Delforge M, Roeloffzen W, Silzle T, Vangsted A, Einsele H, Spencer A, Hajek R, Jurczyszyn A, Lonergan S, Ahmadi T, Liu Y, Wang J, Vieyra D, van Brummelen EMJ, Vanquickelberghe V, Sitthi-Amorn A, de Boer CJ, Carson R, Rodriguez-Otero P, Blade J, Moreau P. A plain language summary of the PERSEUS study of daratumumab plus bortezomib, lenalidomide, and dexamethasone for treating newly diagnosed multiple myeloma. Future Oncol. 2024;20(38):3043-3063. doi: 10.1080/14796694.2024.2394323. Epub 2024 Sep 17.

  PMID: 39287147 DERIVED

• Chari A, Kaufman JL, Laubach J, Sborov DW, Reeves B, Rodriguez C, Silbermann R, Costa LJ, Anderson LD Jr, Nathwani N, Shah N, Bumma N, Holstein SA, Costello C, Jakubowiak A, Wildes TM, Orlowski RZ, Shain KH, Cowan AJ, Pei H, Cortoos A, Patel S, Lin TS, Voorhees PM, Usmani SZ, Richardson PG. Daratumumab in transplant-eligible patients with newly diagnosed multiple myeloma: final analysis of clinically relevant subgroups in GRIFFIN. Blood Cancer J. 2024 Jul 8;14(1):107. doi: 10.1038/s41408-024-01088-6.

  PMID: 38977707 DERIVED

• Callander NS, Silbermann R, Kaufman JL, Godby KN, Laubach J, Schmidt TM, Sborov DW, Medvedova E, Reeves B, Dhakal B, Rodriguez C, Chhabra S, Chari A, Bal S, Anderson LD Jr, Dholaria BR, Nathwani N, Hari P, Shah N, Bumma N, Holstein SA, Costello C, Jakubowiak A, Wildes TM, Orlowski RZ, Shain KH, Cowan AJ, Pei H, Cortoos A, Patel S, Lin TS, Giri S, Costa LJ, Usmani SZ, Richardson PG, Voorhees PM. Daratumumab-based quadruplet therapy for transplant-eligible newly diagnosed multiple myeloma with high cytogenetic risk. Blood Cancer J. 2024 Apr 22;14(1):69. doi: 10.1038/s41408-024-01030-w.

  PMID: 38649340 DERIVED

• Silbermann R, Laubach J, Kaufman JL, Sborov DW, Reeves B, Rodriguez C, Chari A, Costa LJ, Anderson LD Jr, Nathwani N, Shah N, Bumma N, Holstein SA, Costello C, Jakubowiak A, Orlowski RZ, Shain KH, Cowan AJ, Gries KS, Pei H, Cortoos A, Patel S, Lin TS, Voorhees PM, Usmani SZ, Richardson PG. Health-related quality of life in transplant-eligible patients with newly diagnosed multiple myeloma treated with daratumumab, lenalidomide, bortezomib, and dexamethasone: Patient-reported outcomes from GRIFFIN. Am J Hematol. 2024 Jul;99(7):1257-1268. doi: 10.1002/ajh.27326. Epub 2024 Apr 15.

  PMID: 38622840 DERIVED

• Voorhees PM, Sborov DW, Laubach J, Kaufman JL, Reeves B, Rodriguez C, Chari A, Silbermann R, Costa LJ, Anderson LD Jr, Nathwani N, Shah N, Bumma N, Efebera YA, Holstein SA, Costello C, Jakubowiak A, Wildes TM, Orlowski RZ, Shain KH, Cowan AJ, Dinner S, Pei H, Cortoos A, Patel S, Lin TS, Usmani SZ, Richardson PG. Addition of daratumumab to lenalidomide, bortezomib, and dexamethasone for transplantation-eligible patients with newly diagnosed multiple myeloma (GRIFFIN): final analysis of an open-label, randomised, phase 2 trial. Lancet Haematol. 2023 Oct;10(10):e825-e837. doi: 10.1016/S2352-3026(23)00217-X. Epub 2023 Sep 11.

  PMID: 37708911 DERIVED

• Nooka AK, Kaufman JL, Rodriguez C, Jakubowiak A, Efebera Y, Reeves B, Wildes T, Holstein SA, Anderson LD Jr, Badros A, Shune L, Chari A, Pei H, Cortoos A, Patel S, Lin TS, Richardson PG, Voorhees P. A plain language summary of daratumumab plus lenalidomide/bortezomib/dexamethasone in transplant-eligible Black patients with newly diagnosed multiple myeloma in the GRIFFIN study. Future Oncol. 2022 Dec;18(40):4443-4456. doi: 10.2217/fon-2022-0775. Epub 2023 Feb 17.

  PMID: 36799429 DERIVED

• Sborov DW, Baljevic M, Reeves B, Laubach J, Efebera YA, Rodriguez C, Costa LJ, Chari A, Silbermann R, Holstein SA, Anderson LD Jr, Kaufman JL, Shah N, Pei H, Patel S, Cortoos A, Bartlett JB, Vermeulen J, Lin TS, Voorhees PM, Richardson PG. Daratumumab plus lenalidomide, bortezomib and dexamethasone in newly diagnosed multiple myeloma: Analysis of vascular thrombotic events in the GRIFFIN study. Br J Haematol. 2022 Nov;199(3):355-365. doi: 10.1111/bjh.18432. Epub 2022 Sep 16.

  PMID: 36111391 DERIVED

• Swan D, Henderson R, McEllistrim C, Naicker SD, Quinn J, Cahill MR, Mykytiv V, Lenihan E, Mulvaney E, Nolan M, Parker I, Natoni A, Lynch K, Ryan AE, Szegezdi E, Krawczyk J, Murphy P, O'Dwyer M. CyBorD-DARA in Newly Diagnosed Transplant-Eligible Multiple Myeloma: Results from the 16-BCNI-001/CTRIAL-IE 16-02 Study Show High Rates of MRD Negativity at End of Treatment. Clin Lymphoma Myeloma Leuk. 2022 Nov;22(11):847-852. doi: 10.1016/j.clml.2022.07.011. Epub 2022 Jul 21.

  PMID: 35985959 DERIVED

• Voorhees PM, Rodriguez C, Reeves B, Nathwani N, Costa LJ, Lutska Y, Bobba P, Hoehn D, Pei H, Ukropec J, Qi M, Lin TS, Richardson PG. Daratumumab plus RVd for newly diagnosed multiple myeloma: final analysis of the safety run-in cohort of GRIFFIN. Blood Adv. 2021 Feb 23;5(4):1092-1096. doi: 10.1182/bloodadvances.2020003642.

  PMID: 33606004 DERIVED

• Voorhees PM, Kaufman JL, Laubach J, Sborov DW, Reeves B, Rodriguez C, Chari A, Silbermann R, Costa LJ, Anderson LD Jr, Nathwani N, Shah N, Efebera YA, Holstein SA, Costello C, Jakubowiak A, Wildes TM, Orlowski RZ, Shain KH, Cowan AJ, Murphy S, Lutska Y, Pei H, Ukropec J, Vermeulen J, de Boer C, Hoehn D, Lin TS, Richardson PG. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020 Aug 20;136(8):936-945. doi: 10.1182/blood.2020005288.

  PMID: 32325490 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Lenalidomide; Bortezomib; Dexamethasone; daratumumab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Limitations and Caveats

Initial protocol did not require minimal residual disease (MRD) testing in all participants, impacting the interpretation of MRD negativity rates in intent-to-treat (ITT) group, which strongly favored daratumumab treatment. Sensitivity analysis, including MRD negativity rate in participants with a complete response (CR) or better and with an informative baseline clone and follow-up MRD testing, were performed and confirmed a strong benefit for daratumumab treatment.

Results Point of Contact

• Title: Clinical Leader
• Organization: Janssen Research & Development, LLC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2016
• First Posted: August 22, 2016
• Study Start: August 29, 2016
• Primary Completion: January 25, 2019
• Study Completion: April 8, 2022
• Last Updated: February 4, 2025
• Results First Posted: February 7, 2020

Record last verified: 2025-01

Locations

US (36)